Renal insufficiency methotrexate

Therapy with leucovorin/5-FU must not be initiated or continued in patients who have symptoms of Gl toxicity of any severity, until those symptoms have completely resolved. Patients with diarrhea must be monitored with particular care until the diarrhea has resolved, as rapid clinical deterioration leading to death can occur. Methotrexate concentrations Monitoring of the serum methotrexate concentration is essential in determining the optimal dose and duration of treatment with leucovorin. Delayed methotrexate excretion may be caused by a third space fluid accumulation, renal insufficiency, or inadequate hydration. Under such circumstances, higher doses of leucovorin or prolonged administration may be indicated. Doses higher than those recommended for oral use must be given IV. 

In patients with psoriasis treated with methotrexate, hepatic damage is common however, among patients with inflammatory bowel disease and rheumatoid arthritis, the risk is significantly lower. Renal insufficiency may increase risk of hepatic accumulation and toxicity. 

In studies of the neurotoxic effects of low-dose methotrexate treatment, dizziness, headache, visual disturbances or hallucinations, lack of concentration, cognitive dysfunction, and depression-like symptoms were detected in 1-35% of patients (527,528). Advanced age and mild renal insufficiency were possible susceptibility factors (529). 

Strong association Previous or concurrent heavy alcohol use Pre-existing liver disease Daily methotrexate administration Renal insufficiency... 

When serum methotrexate concentrations are high, leu-covorin (folinic acid) rescue may protect against renal damage. Methotrexate concentrations are only transiently lowered by hemoperfusion, and they are unaffected by peritoneal dialysis once there is acute renal insufficiency. Sustained reductions in drug concentrations and recovery of renal function have been reported after charcoal hemoperfusion followed by hemodialysis (63,64). 

Maiche AG, Lappalainen K, Teerenhovi L. Renal insufficiency in patients treated with high dose methotrexate. Acta Oncol 1988 27(l) 73-4. 

Molina R, Fabian C, Cowley B Jr. Use of charcoal hemo-perfusion with sequential hemodialysis to reduce serum methotrexate levels in a patient with acute renal insufficiency. Am J Med 1987 82(2) 350-2. 

Urinary tract Methotrexate-induced renal damage appears to be physicochemical in nature. Both the parent compound and its major metabolite, 7-hydroxymethotrexate, are less soluble at acidic pH values, increasing the risk of precipitation in the kidneys, particularly at high dosages. An amorphous yellow material—very probably methotrexate—has been isolated in the kidneys of patients who died as a result of methotrexate-induced renal dysfunction. For physicochemical reasons, it is recommended that the urine be alkalinized (target urinary pH above 7.5) before intensive methotrexate regimens are started. Supportive agents include sodium bicarbonate orally or intravenously, acetazolamide 500 mg qds, or both in combination [1805, 18F, 182 ]. If there is acute renal insufficiency despite appropriate urinary alkalinization, one may need to use carboxypeptidase G2 as an antidote, which is also appropriate in cases of accidental intrathecal overdose of methotrexate [183", 184 ]. 

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